Aims: 1) To identify environmental risk factors for specific leukemia subgroups defined by morphology and cytogenetics. 2) To identify environmental risk factors for myelodysplasia. 3) To identify associations between environmental exposures and somatic mutations in acute leukemia.4) To identify groups with increased susceptibility for developing acute leukemia. Accomplishments: Despite extensive study, the role of low-dose environmental exposures in the etiology of acute leukemia remains controversial. Our study is the first large-scale study to include evaluation of risk factors for specific subtypes of leukemia defined by chromosome abnormalities and molecular changes. Our results suggest that genetic factors may help to define groups who are uniquely susceptible to developing leukemia following environmental insult. This may provide a new focus for studies of risk factors for acute leukemia. Our data also suggest that the pathogenesis of leukemia due to chemical exposures may be distinct from leukemia related to other causes. Family history is a complex measure that reflects the effects of possibly multiple susceptibility genes and shared environmental exposures. Although the trend has been to focus on specific known gene polymorphisms or the interactions between known exposures and multiple known genes, an association between family history and risk may lead to the generation of new hypotheses. As a measure of the combined impact of several genes and exposures, family history may in fact be a more sensitive indicator of enhanced susceptibility to risks from specific toxic exposures. Most studies of cancer prognosis and treatment outcome focus on tumor characteristics (e.g. grade, stage) and treatments. Host factors such as nutritional status, use of medications, and continued exposure to carcinogens (e.g. smoking) may also affect outcome. We have a unique opportunity to address this because patients included in this study were enrolled at the time they entered randomized treatment studies. Their treatments and tumor factors are well documented and can be controlled for in our analysis.